Guanqing Yang, Jianxun Ding
Immunotherapy has revolutionized cancer therapy, while its clinical outcomes remain limited by poor targeting, insufficient immune activation, and adverse side effects. Bioactive poly(amino acid) nanomaterials offer a versatile platform to address these challenges owing to their tunable molecular structures, modular composition, bioresponsiveness, and inherent chirality. Understanding the structure-activity relationships enables the rational design of poly(amino acid)-based nanomaterials that enhance immunotherapeutic efficacy while minimizing systemic toxicity. This review discusses recent advances in our group in using bioactive poly(amino acid) nanomaterials to enhance anti-cancer immunity. Four major strategies are emphasized, including inducing immunogenic cell death, constructing cancer nanovaccines, reversing tumor immune escape, and reprogramming cancer cell metabolism. These approaches act synergistically to improve therapeutic efficacy and safety. Furthermore, design principles and translational prospects are discussed, providing a framework for the development of next-generation nanomaterials in cancer immunotherapy.